Durable Remissions in Metastatic Breast Cancer With ABMT

Durable Remissions in Metastatic Breast Cancer With ABMT

MIAMI BEACHUse of aggressive induction therapy followed by
high-dose chemotherapy with autologous bone marrow transplantation
(ABMT) yielded a 40% complete remission rate among 425 women with
metastatic breast cancer treated at Duke University Medical Center.
Of these women, 11% remained in complete remission 5 years after
therapy, David A. Rizzieri, MD, reported at the 40th Annual Meeting
of the American Society of Hematology (ASH).

Noting that the Duke results compare favorably with those of
currently available standard therapies, Dr. Rizzieri characterized
the ability of this intensive regimen to produce durable remissions
in patients with metastatic breast cancer as a baby step
forward for high-dose therapy.

The median age of patients participating in the study was 43 years;
306 were premenopausal; and 10% were African-Americans or another
nonwhite ethnic group. More than 40% of the women (180 patients) had
lung or pleural metastases, and 147 had liver involvement. More than
half of the participants (250) had two or more sites of metastasis.
None of the patients had received prior chemotherapy for metastatic disease.

Thus, the women were fairly representative of metastatic breast
cancer patients and not a highly select group, Dr. Rizzieri told
Oncology News International in an interview.

Treatment Regimen

The participants first received 2 to 4 cycles of the Duke AFM
regimenfluorouracil (750 mg/m²/d infused continuously for
5 days), doxorubicin (250 mg/m² on days 3 through 5), and
methotrexate (250 mg/m² for 10 minutes on day 15, with
leucovorin rescue if necessary).

Patients who responded completely to AFM were randomized to immediate
high-dose therapy plus ABMT or were followed very closely (every 6
weeks) and given high-dose therapy at the first sign of relapse.
Women who had only a partial response to the induction regimen
underwent immediate high-dose therapy, while those whose disease did
not respond or progressed were taken off study and followed for survival.

The preparative regimen used in this study was STAMP 1, consisting of
cyclophosphamide (1,875 mg/m² on days -6 through -4), cisplatin
(55 mg/m² via continuous infusion on days -6 through -4), and
carmustine (600 mg/m² delivered at a rate of 5 mg/m²/min on
day -3).

Overall, 315 (74%) of the 425 women responded to AFM, 113 with a
complete response and 202 with a partial response. Of the 315
patients who responded to induction therapy, 299 (100 complete and
199 partial responders) actually received high-dose therapy plus ABMT.

At the end of the entire treatment regimen, 40% of patients (171/425)
were in complete remission. Of the 299 patients who underwent
high-dose therapy, 58% (171/299) attained a complete remission. This
complete remission rate, Dr. Rizzieri told ONI, is higher than that
achieved with standard chemotherapy, although not significantly so.

He added, We were able to convert one-third of patients who had
a partial response to induction therapy to actual complete response
with high-dose therapy, characterizing this as a
significant conversion rate.

CRs Maintained Over the Long Term

Even more important, Dr. Rizzieri said, was that women whose disease
responded completely to the intensive regimen stayed in remission
over the long term. Of all 425 patients enrolled in the study, 11%
remained in complete remission at 5 years. Among the subgroup of
patients who responded to AFM and received ABMT, 16% were alive and
still completely free of disease at the 5-year mark (for an overall
survival rate of 20%). The smaller subgroup of patients who had a
complete response to AFM and remained in remission after high-dose
therapy enjoyed a 20% progression-free survival rate at 5 years and a
38% overall survival rate.

When asked whether the Duke group uncovered any characteristics that
could be used to identify patients who maintained remission over the
long term. Dr. Rizzieri said that women with liver metastases
appeared to have a worse outcome than did those with nonvisceral
sites of metastasis. However, he said, these are patients with
liver metastases who remain in long-term remission. Other
factors predictive of a poor prognosis, he said, were the failure of
prior adjuvant therapy and a short duration of first complete response.

Dr. Rizzieri noted that there were no statistically significant
differences between women randomized to immediate vs delayed
transplant. Thus, it would not be unreasonable for a
patient with newly diagnosed metastatic breast cancer to receive
standard chemotherapy and, if a remission is obtained, be monitored
closely for signs of relapse, and then given high-dose therapy if
such signs were observed.

However, given that most patients will relapse eventually, Dr.
Rizzieri believes that high-dose therapy has a better chance for
success if started when the patient is in remission rather than after
relapse, as new protocols are focusing on manipulation of minimal
residual disease post-transplant.

Your name

E-mail

The content of this field is kept private and will not be shown publicly.